The Shengmai San Exerts Therapeutic Effects on Type 2 Diabetes by Modulating the PI3K/AKT/GSK3B Signaling Pathway

Hongchao Shang, Tianyu Wang, Daoran Pang, Yue Qi, Lu Liu, Yifei Wang, Yan Gao Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of ChinaCorrespondence: Yan Gao, Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of China, Tel +18615212592, Email [email protected]: Shengmai San (SMS) is a traditional Classic Recipes made with Panax ginseng, Ophiopogon, and Schisandra. The precise mechanism of action of SMS remains unclear, despite its noteworthy therapeutic advantages for type 2 diabetes mellitus (T2DM).Objective: The objective of this study was to confirm the mechanism of SMS in the treatment of T2DM.Materials and Methods: UPLC-MS/MS was employed to identify the active components in SMS. Using network pharmacology, the intervention pathways of SMS in T2DM rats were investigated. A high-sugar, high-fat diet and intrabitoneal injection of streptozotocin were used to create a T2DM rat model. The serum parameters of each group were assessed following the completion of the experiment. The mRNA and protein expression levels of genes related to the PI3K/AKT/GSK3B pathway were analyzed using qRT-PCR and Western blot.Results: There were 39 components found in SMS San by UPLC-Q-Orbitrap/MS. Network pharmacology and molecular docking study indicate that the PI3K/AKT/GSK3B pathway may be a part of SMS’s therapeutic mechanism for the treatment of T2DM. Rats’ serum levels of TC, TG, LDL-C, MDA, TNF-α, and IL-6 dramatically dropped after taking SMS, whereas SOD and HDL-C levels rose. The improvement of these parameters may be related to SMS activation of downstream target proteins, PI3K, and AKT.Conclusion: SMS can help cure T2DM mellitus by regulating the PI3K/AKT/GSK3B pathway, improving islet tissue injury, reducing oxidative stress, and easing lipid metabolism issues. This study not only revealed the unique therapeutic mechanism of SMS by regulating the PI3K/AKT/GSK3β signaling pathway, but also provided new theoretical support for multi-target and personalized treatment of diabetes. Its novelty lies in the first exploration of the mechanism of action of traditional Chinese medicine prescriptions through the lens of modern molecular biology, emphasizing the potential of natural medicines in diabetes treatment. Keywords: Shengmai San, network pharmacology, UPLC-MS/MS, type 2 diabetes mellitus, PI3K/AKT/GSK3B pathway